Journal of Veterinary Clinics (한국임상수의학회지)

The Korean Society of Veterinary Clinics (한국임상수의학회)
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Effect on the Inhibition of DNA-PK in Breast Cancer Cell lines(MDA-465 and MDA-468) with DNA-PKcs Binding Domain Synthetic Peptide of Ku80

Ku80의 DNA-PKcs 결합부위 합성 Peptide 투여에 의한 유방암세포의 DNA-dependent protein kinase 억제 효과

  • 김충희 (진주산업대학교 동물생명과학과) ;
  • 김태숙 (진주산업대학교 동물생명과학과) ;
  • 문양수 (진주산업대학교 동물생명과학과) ;
  • 정장용 (진주산업대학교 동물생명과학과) ;
  • 강정부 (경상대학교 수의과대학) ;
  • 김종수 (경상대학교 수의과대학) ;
  • 강명곤 (건국대학교 수의과대학) ;
  • 박희성 (진주산업대학교 동물생명과학과)
  • Published : 2004.09.01
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Abstract

DNA double-strand break (DSB) is a serious treat for the cells including mutations, chromosome rearrangements, and even cell death if not repaired or misrepaired. Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) bound to double strand DNA breaks are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and the interaction is essential for DNA-dependent protein kinase (DNA-PK) activity. The Ku80 mutants were designed to bind Ku70 but not DNA end binding activity and the peptides were treated in breast cancer cells for co-therapy strategy to see whether the targeted inhibition of DNA-dependent protein kinase (DNA-PK) activity sensitized breast cancer cells to ionizing irradiation or chemotherapy drug to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. We designed domains of Ku80 mutants, 26 residues of amino acids (HN-26) as a control peptide or 38 (HNI-38) residues of amino acids which contain domains of the membrane-translocation hydrophobic signal sequence and the nuclear localization sequence, but HNI-38 has additional twelve residues of peptide inhibitor region. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, resulting in inactivation of DNA-PK complex activity in breast cancer cells (MDA-465 and MDA-468). Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to irradiation or chemotherapy drugs. The growth of breast cancer cells was also inhibited. These results demonstrate the possibility of synthetic peptide to apply breast cancer therapy to induce apoptosis of cancer cells.

Keywords

References

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